Drug Release And Dissolution Flashcards
What are the different disintegration test throughout the years
• 1950: Disintegration tests became official in the USP.
They are indirectly related to drug bioavailability and
product performance.
• 1962: became known that dissolved drug is necessary
for physiological action the need for dissolution
requirement in capsule and tablet monographs of drugs
having aqueous solubility below 1% was recognized.
• 1968: The USP dissolution apparatus I (basket method)
was officially adopted.
• 1978: The USP dissolution apparatus II (paddle method)
was officially adopted.
• Now there are USP dissolution apparatuses III
and IV, as well.
• Dissolution testing is used to study drug release
in vitro.
• Nowadays, dissolution testing is essential in
quality control (QC) of drug products
What are the different dosage forms that are characterized by release in vitro
by release in vitro:
- Solid oral dosage forms: tablets, chewable
tablets, enteric coated tablets, capsules,
caplets, encapsulated beads, and gelcaps.
- Rectal dosage forms (suppositories)
- Pulmonary dosage forms
- Modified release dosage forms
- Semisolid products (ointments, creams and
transdermal products).
What is a drug substance and what is the drug product
• Drug substance: active pharmaceutical ingredient (API)
that is intended to furnish a pharmacological activity.
• Drug product: is the finished dosage form (capsule,
tablet…etc) that contain a drug substance, generally, but
not necessarily in association with one or more
ingredient.
What is drug release
It is the process by which the drug substance leaves
the drug product and is subjected to absorption,
distribution, metabolism, and excretion (ADME)
What are the different classes of drug release
– Immediate release: allows the drug to dissolve in the
GIT contents with no intention of delaying or
prolonging the dissolution or absorption of the drug.
– Modified release: dosage forms whose drug-release
characteristics of time course and/or location are
chosen to accomplish therapeutic or convenience
objectives not offered by solutions or immediate
release dosage forms.
modified- release products include: delayed (enteric
coated products) and extended-release products
(controlled release)
– Enteric coated products: intended to delay the
release of the drug until the dosage form has
passed through the stomach. Enteric coated
products = delayed release dosage forms.
– Extended-release products: they are
formulated to make the drug available over an
extended period after ingestion this allows
a reduction in dosing frequency compared to
immediate release products.
What is dissolution
It is the process by which a solid phase goes into solution
phase.
The release of drug from a solid dosage
form consists of the following steps:
1) Wetting of solid dosage form
2) Penetration of the solvent into the
formulation
3) Swelling
4) Disintegration and disaggregation
5) Dissolution
When and Why dissolution is important?
It is always important. However, it of utmost
importance in the case of poorly-soluble drugs.
Because dissolution will be the limiting or rate-
controlling step in the absorption of drug as it is the
slowest step in the various stages involved in the
release of the drug from its dosage form and it
passage into the systemic circulation.
What is the noyes-whitney model
DM/et= DA/H (Cs-Cb)
M: mass of solute dissolved at time = t.
dM/dt: rate of dissolution.
D: diffusion coefficient of the solute in solution.
A: surface area of exposed solid
h: thickness of diffusion layer.
Cs
: solubility of the drug (concentration of a saturated
solution of the drug)
Cb
: concentration of the drug in the bulk solution at
time = t.
• Note: sink condition applies for absorption from GIT and
therefore, Cb = 0.
What factors affect dissolution according to
the Noyes-Whitney equation:
– Diffusion coefficient of the solute in solution.
– Surface area of exposed solid
– Thickness of diffusion layer.
– Solubility of the drug
The only one that we can control is the surface area, by changing the particle size
The rate and extent of drug absorption are
determined by:
– The rate of drug release and dissolution
relative to the rate of transit through the
intestine.
– The permeability profile of the small intestine
to the drug.
If drug dissolution is slower than absorption
less drug will be absorbed
What is the role dissolution tests in pharmaceutics
– Development of new products
– Quality control
– Assist in determination of bioequivalence.
For two products (e.g., generic versus brand) to
be bioequivalent they ought to have similar
dissolution profiles.
– In case of drug products belonging to class I:
similar dissolution is enough to assure
bioequivalence. No need to perform clinical
studies (you will save $$$)
What are the physiochemical and physiological factors that we need to control in dissolution tests
– The composition of GIT fluid
– Mixing patterns (hydrodynamics) in GIT.
– Volume of the contents in the GIT
What is the composition effect
– Presence of food will raise the pH of the stomach
from 1-3 units to 5.5-7 units. This will affect the
solubility of the drug
– Food will affect the viscosity of GIT fluid and thus the
diffusivity of the drug in that fluid.
– Surfactants are known to increase wettability of
drugs by lowering surface tension. ↑ wettability ↑
dissolution rate.
Natural surfactants include: bile salts and lecithins
(phospholipids).
the level of surfactants can vary according to the
fed-state of the patient.
• Biorelevant media for dissolution has been proposed:
– Simulated gastric fluid (SGF) and Simulated
intestinal fluid (SIF) : two different media were
proposed:
– Fed state
– Fasted state
What’s a method
lets define a method. The
method is a function of two factors:
– Medium composition
– Stirring dynamics
• In pharmaceutical industry, we must use a
discriminating method.
– Not under-discriminating
– Not over-discriminating
What is an over discriminating method
the method show different
dissolution profile although the two formulation
have similar bioavailability
